Acute and long-term effects of thyrotropin releasing hormone on behavior mediated by dopaminergic and cholinergic activities in mice.

Abstract

Acute and long-term (3 weeks) effects of thyrotropin releasing hormone (TRH) on behavior were investigated in mice. A single injection of TRH produced Straub tail, tremor and salivation, as well as stereotyped responses, such as head bobbing, jaw movement, digging and sniffing. Dose- and time-dependency for the effects of TRH were different depending on each response. A single injection of TRH at a low dose of 2.5 mg/kg SC did not produce stereotypy but this behavior was induced when this dose of TRH was administered in combination with atropine (3 mg/kg IP). In addition, a single low dose of TRH elicited tremor and salivation which were potentiated by physostigmine (0.1 mg/kg IP). A single high dose (20 mg/kg IP) produced marked tremor and salivation which were conversely blocked by atropine. Following daily administration of TRH at a low dose of 2.5 mg/kg SC for 21 days, stereotyped behavior was progressively increased whereas tremor and salivation were decreased. This increase in stereotyped behavior was inhibited by haloperidol (1 mg/kg IP) or physostigmine (0.1 mg/kg IP). When saline was administered instead of TRH for 3 days after long-term administration of TRH, sterotyped behavior was maintained for 2 days but thereafter decreased to some extent. When TRH (1.25 mg/kg SC) was again administered at this stage, there was a marked increase in sterotyped response. These results suggest that TRH induces dopaminergic activation, accompanied by both cholinergic inhibition and cholinergic activation, and that the former is potentiated while the latter is reduced after daily administration of TRH.